FIG. 6.

Overexpression of LIPIN2 perturbs hepatic insulin signaling in DIO mice. A–C: Glucose tolerance test (A) (2 g glucose per kg body wt, n = 6 for GFP and n = 7 for wild-type and mutant LIPIN2, using 16-h fasted mice at day 4 after adenoviral injection), plasma insulin levels during glucose tolerance test (B), and insulin tolerance test (C) (1 unit insulin per kg body wt, n = 8 for GFP and mutant LIPIN2 mutant, and n = 9 for wild-type LIPIN2, at day 5 after adenoviral injection) from mice as in Fig. 5. D: Western blot assay using lysates from Ad GFP, Ad wild-type LIPIN2 (L2 wt), or Ad mutant LIPIN2 (L2 mut) infected mouse livers as in Fig. 5. PBS (for control) or insulin (0.5 unit/kg body wt) was injected intraperitoneally for 10 min before the collection of liver for Western blot assays on day 7 after adenoviral injection. Representative data from three independent experiments (n = 6 for each condition) are shown. E: A proposed model for ER stress–induced activation of LIPIN2 in promoting DAG production and the perturbation of hepatic insulin signaling. Error bars indicate SEM. Statistical significance was assessed by two-tailed Student t test. *P < 0.05; **P < 0.01; †P < 0.05; ‡P < 0.01.